A detailed knowledge of the processes involved in the formation of synapses is one of the prerequisites for studying the problem of how specific connections are established between nerve cells in the developing brain. Many of our present concepts about synapse formation have been derived from studies on a regenerating adult peripheral synapse, the neuromuscular junction. We are studying the motor nerve terminal - the presynaptic-element of the neuromuscular synapse - as it progresses from a growing process to attain its final form, highly specialized for synaptic transmission. The cutaneous pectoris muscle of the frog its well suited for studies on the precision of reinnervation. It is thin and transparent which enables one to use quantitative light microscopic techniques on entire neuromuscular junctions in whole mounts and to examine the details of specific sites by electron microscopy. During the past year we considered two questions: a) how much of the original subsynaptic membrane is covered by regenerating nerve terminals, and b) how much of the neuromuscular contact is formed de novo. Our objective for the next year is to determine the sequence of differentiation along the length of terminal branches of regenerating motor axons in the frog. We will examine various points along individual branches wth regard to four different parameters; a) size and shape; b) organization of organelles; c) stimulus-induced endocytosis; and d) release of transmitter. We will also seek to determine whether the onset and development of synaptic transmission occur at anatomically definable stages in the reformation of terminal arborizations. BIBLIOGRAPHIC REFERENCES: Letinsky, M., Fischbeck, K. and McMahan, U.J. (1976) Precision of reinnervation of original postsynaptic sites in muscle after a nerve crush. J. Neurocytol. 5,691-71 Rotshenker, S. and McMahan, U.J. (1976) Altered patterns of innervation in frog muscle after denervation, J. Neurocytol. 5, 719-750.